Knox implementation of Destexhe 1998 spike and wave oscillation model (Knox et al 2018)

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" ...The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE. METHODS: The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABAA , and GABAB synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABAA conductance. RESULTS: Decreasing cortical GABAA conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right shift reduced network propensity for oscillations of any type...."
1 . Knox AT, Glauser T, Tenney J, Lytton WW, Holland K (2018) Modeling pathogenesis and treatment response in childhood absence epilepsy. Epilepsia 59:135-145 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Neocortex; Thalamus;
Cell Type(s): Thalamus reticular nucleus GABA cell; Thalamus geniculate nucleus/lateral principal GLU cell; Hodgkin-Huxley neuron; Neocortex layer 4 pyramidal cell; Neocortex fast spiking (FS) interneuron;
Channel(s): I h; I Na,t; I K,leak; I T low threshold; I M;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA;
Simulation Environment: NEURON;
Model Concept(s): Spindles; Oscillations;
Implementer(s): Knox, Andrew [knox at]; Destexhe, Alain [Destexhe at];
Search NeuronDB for information about:  Thalamus geniculate nucleus/lateral principal GLU cell; Thalamus reticular nucleus GABA cell; GabaA; GabaB; AMPA; I Na,t; I T low threshold; I K,leak; I M; I h;
cadecay.mod *
HH2.mod *
Ih.mod *
IT.mod *
IT2.mod *
kleak.mod *
mosinit.hoc *

	One compartment model and currents derived from:

	Destexhe, A., Contreras, D., Sejnowski, T.J. and Steriade, M.
	A model of spindle rhythmicity in the isolated thalamic reticular
	nucleus.  J. Neurophysiol. 72: 803-818, 1994.

	Destexhe, A., Contreras, D., Steriade, M., Sejnowski, T.J.,
	and Huguenard, J.R.  In vivo, in vitro and computational analysis of 
	dendritic calcium currents in thalamic reticular neurons.  
	Journal of Neuroscience 16: 169-185, 1996.


	- passive parameters estimated from simplex
	- IT2: Q10=2.5, strong conductance for broad bursts
	- no IK[Ca], no ICAN
	- Ca++: simple decay only

	This model is described in detail in:

	Destexhe, A., Bal, T., McCormick, D.A. and Sejnowski, T.J.
	Ionic mechanisms underlying synchronized oscillations and propagating
	waves in a model of ferret thalamic slices. Journal of Neurophysiology
	76: 2049-2070, 1996.
	See also ,

	Alain Destexhe, Salk Institute and Laval University, 1995


print " "
print " << defining template for one-compartment sRE cell >> "
print " "

begintemplate sRE		// create a new template object
public soma, ampapost, gabaapost, PYlist, TClist, REgabaalist

objectvar ampapost, gabaapost, PYlist, TClist, REgabaalist

create soma[1]			// one-compartment of 14260 um2
soma {
  nseg = 1
  diam = 70
  L = 64.86

proc init() { local v_potassium, v_sodium

  v_potassium = -100		// potassium reversal potential 
  v_sodium = 50			// sodium reversal potential 

  soma {
	Ra = 100		// geometry 
	nseg = 1
	diam = 70
	L = 64.86

	insert pas		// leak current 
	e_pas = -90
	g_pas = 5e-5        //5e-5

	insert hh2		// Hogin-Huxley INa and IK 
	ek = v_potassium
	ena = v_sodium
	vtraub_hh2 = -55
	gnabar_hh2 = 0.2  //original value
	gkbar_hh2 = 0.02

	insert itrecustom 	// ret. IT current - custom channel
	proportion_custom = 0
	taubase_itrecustom = 85
	shift_itrecustom = 2
	qm_itrecustom = 2.5		// low q10
	qh_itrecustom = 2.5
	gcabar_itrecustom = proportion_custom * 0.003	// strong

	insert it2 		// reticular IT current - whole cell
	cai = 2.4e-4 
	cao = 2 
	eca = 120 
	shift_it2 = 2
	taubase_it2 = 85
	qm_it2 = 2.5		// low q10
	qh_it2 = 2.5
	gcabar_it2 = (1-proportion_custom) * 0.003	// strong
	//gcabar_it2 = 0.003	// strong - original

	insert cad		// calcium decay
	depth_cad = 1
	taur_cad = 5
	cainf_cad = 2.4e-4
	kt_cad = 0		// no pump

	PYlist = new List()
	TClist = new List()
	REgabaalist = new List()

	ampapost = new AMPA_S(0.5)
	gabaapost = new GABAa_S(0.5)

  print " "
  print "<< sRE: passive, INa, IK, ITs, IAHP and Ca++ decay inserted >>"
  print " "

endtemplate sRE

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